Arthropod pests are one of the major threats to human welfare and exert continued stress on the food supply via herbivory, fouling and disease transmission. Synthetic insecticides played a significant role and, in many ways, ushered in modern agriculture and pest control. However, there is increasing pressure from the public and from regulatory agencies to reduce or eliminate the exclusive use of synthetic chemical in the control of agricultural arthropod pests. The widespread use of available insecticides has resulted in the development of resistant insect populations. Insecticide resistance is a complex phenomenon manifested in a diverse array of physiological and/or behavioral mechanisms. Major mechanisms that are responsible for the development of insecticide resistance are metabolic detoxification, target site mutation, reduced cuticular penetration and behavioral avoidance. Novel classes of natural insecticides are needed to combat the ever-increasing number of resistant insect species and populations.
Indole-diterpenes are a natural, structurally diverse group of secondary metabolites with a common cyclic diterpene backbone derived from geranylgeranyl diphosphate and an indole group derived from indole-3-glycerol phosphate. Terpendoles are a specific class of indole-diterpene alkaloids produced by fungi that were first discovered by Huang et al. when screening for acyl-CoA:cholesterol acyltransferase inhibitors. Huang et al. Terpendoles, Novel ACAT inhibitors produced by Albophoma yamanashiensis I. production, isolation and biological properties, J Antibiot (Tokyo). 1995 January, 48(1), 1-4. Specifically, Huang et al. discovered terpendoles A-D. Since that time, 10 additional terpendoles have been described in the literature and termed terpendoles E-M. To date, terpendoles have been further discovered to inhibit motor activation of mitotic kinesin Eg5. See, Nakazawa J. et al., A novel action of terpendole E on the motor activity of mitotic Kinesin Eg5, Chem Biol, 2003 February, 10(2), 131-137. Due to its role in inhibition mitotic kinesin, terpendole E is currently being researched as a possible anti-cancer drug. However, there is no known application of terpendoles that would benefit humans.
Given that there is currently no known use for terpendoles and also given that resistance is problematic for insect pest populations, we assert that there is a need in the art for novel uses of terpendoles as natural pesticides.